Journal article

GGA1 regulates signal-dependent sorting of BACE1 to recycling endosomes, which moderates A beta production

Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson

MOLECULAR BIOLOGY OF THE CELL | AMER SOC CELL BIOLOGY | Published : 2018

Abstract

The diversion of the membrane-bound β-site amyloid precursor protein-(APP) cleaving enzyme (BACE1) from the endolysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the sorting nexin 4 (SNX4)-mediated, signal-independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the DXXLL-motif sequence DISLL in the cytoplasmic tail of BACE1. The phosphomimetic ..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

Confocal microscopy was performed at the Biological Optical Microscopy Platform (BOMP) at the University of Melbourne. We thank Rohan Teasdale (University of Queenland) and Peter Cullen (University of Bristol) for SNX4 and Vps26A constructs, respectively. This work was supported by funding from the National Health and Medical Research Council (APP1082600). We thank Fiona Houghton for expert technical advice.